Monocyte surface expression of Fcgamma receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus.
Monocyte surface expression of Fcgamma receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus.
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DOI：
10.1186/ar3017
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发表时间：
2010
影响因子：
4.9
通讯作者：
Reeves WH
中科院分区：
文献类型：
--
作者：
Li Y;Lee PY;Kellner ES;Paulus M;Switanek J;Xu Y;Zhuang H;Sobel ES;Segal MS;Satoh M;Reeves WH
超过一半的系统性红斑狼疮 (SLE) 患者表现出 I 型干扰素 (IFN-I) 产生过多的证据，这是一种与肾脏疾病和某些自身抗体相关的表型。然而，血清中 IFN-I 蛋白的检测并不可靠，并且干扰素刺激基因 (ISG) 表达的测量既昂贵又耗时。本研究的目的是确定临床样本中 IFN-I 活性的替代标记物，用于监测疾病活动和治疗反应。使用流式细胞术分析 SLE 患者和健康对照者全血中 Fcγ 受体 (FcγR)、趋化因子受体和激活标记物的单核细胞表面表达。还测量了与 Toll 样受体 (TLR) 激动剂、细胞因子或 SLE 患者血清培养的健康对照的外周血单核细胞 (PBMC) 中的 FcγR 表达。通过实时 PCR 分析 ISG 的表达。 SLE 患者的循环 CD14+ 单核细胞显示 FcγRI (CD64) 表面表达增加。 CD64 染色的平均荧光强度与 ISG 表达（MX1、IFI44 和 Ly6E）高度相关。在体外，IFN-I以及TLR7和TLR9激动剂诱导健康对照的单核细胞表达CD64。将健康对照的单核细胞暴露于 SLE 血清也以 IFN-I 依赖性方式上调 CD64 的表达。高剂量皮质类固醇治疗后，观察到 CD64 表达减少，同时 ISG 表达减少。循环单核细胞上CD64的表达是IFN-I诱导的并且与ISG表达高度相关。流式细胞术分析循环单核细胞上的 CD64 表达是估计 SLE 患者中 IFN-I 水平的便捷且快速的方法。
More than half of systemic lupus erythematosus (SLE) patients show evidence of excess type I interferon (IFN-I) production, a phenotype associated with renal disease and certain autoantibodies. However, detection of IFN-I proteins in serum is unreliable, and the measurement of interferon-stimulated gene (ISG) expression is expensive and time consuming. The aim of this study was to identify a surrogate marker for IFN-I activity in clinical samples for monitoring disease activity and response to therapy. Monocyte surface expression of Fcγ receptors (FcγRs), chemokine receptors, and activation markers were analyzed with flow cytometry in whole blood from patients with SLE and healthy controls. FcγR expression also was measured in peripheral blood mononuclear cells (PBMCs) from healthy controls cultured with Toll-like receptor (TLR) agonists, cytokines, or serum from SLE patients. Expression of ISGs was analyzed with real-time PCR. Circulating CD14+ monocytes from SLE patients showed increased surface expression of FcγRI (CD64). The mean fluorescent intensity of CD64 staining correlated highly with the ISG expression (MX1, IFI44, and Ly6E). In vitro, IFN-I as well as TLR7 and TLR9 agonists, induced CD64 expression on monocytes from healthy controls. Exposure of monocytes from healthy controls to SLE sera also upregulated the expression of CD64 in an IFN-I-dependent manner. Decreased CD64 expression was observed concomitant with the reduction of ISG expression after high-dose corticosteroid therapy. Expression of CD64 on circulating monocytes is IFN-I inducible and highly correlated with ISG expression. Flow-cytometry analysis of CD64 expression on circulating monocytes is a convenient and rapid approach for estimating IFN-I levels in SLE patients.
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影响因子：
8.8
作者：
Nuutila, Jari;Hohenthal, Ulla;Lilius, Esa-Matti
通讯作者：
Lilius, Esa-Matti
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
4.9
作者：
Li Y;Lee PY;Sobel ES;Narain S;Satoh M;Segal MS;Reeves WH;Richards HB
通讯作者：
Richards HB
影响因子：
4.4
作者：
Lee, Pui Y.;Weinstein, Jason S.;Reeves, Westley H.
通讯作者：
Reeves, Westley H.
影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J